Human immunodeficiency virus (HIV-1) is the major cause of acquired immunodeficiency syndrome (AIDS) in humans. The HIV-1 envelope glycoproteins, gp120 and gp41, are contained in trimeric complexes on the virion surface. The gp120 envelope glycoprotein mediates virus attachment to target cell receptors, CD4 and the chemokine receptors, CCR5 or CXCR4. The interaction of gp120 with CD4 is understood at the atomic level of resolution whereas the interaction of gp120 with the chemokine receptors has been studied by mutagenesis and the use of model peptides. Receptor binding triggers conformational changes in the HIV-1 envelope glycoproteins leading to the fusion of the viral and target cell membranes, a process mediated by the gp41 transmembrane envelope glycoprotein. The HIV-1 envelope glycoproteins and receptors represent potential targets for pharmacologic intervention. The purpose of the Virology Core (Core A) is to provide Program investigators with assays that measure the efficacy with which candidate antiviral molecules interfere with virus-receptor interactions. The specific aims of the Virology Core are: 1) To develop reagents that mimic native HIV- 1 envelope glycoproteins and receptors; 2) To develop and perform assays for blockade of HIV- 1 receptor binding; 3) To test antiviral activity of primary lead compounds; and 4) To derive and characterize drug-resistant viruses.